BackgroundThe aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis.Methodology/Principal FindingsExpression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot.ResultsThe expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment.ConclusionOverexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells.

Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo. Mechanistically, inhibition of PLOD2 inactivated PI3K/AKT signaling pathway and thus regulated the expression of its downstream epithelial–mesenchymal transition (EMT)-associated regulators, including E-cadherin, vimentin, N-cadherin, β-catenin, snail and slug in glioma cells. Moreover, PLOD2 could be induced by hypoxia-inducible factor-1α (HIF-1α) via hypoxia, thereby promoting hypoxia-induced EMT in glioma cells. Our data suggests that PLOD2 may be a potential therapeutic target for patients with glioma.

Radical surgery was recommended as the optimal treatment for nongerminomatous pineal region tumors. Favorable results could be achieved by experienced neurosurgeons. Hydrocephalus could be cured by radical tumor removal in the majority of cases. The occipital transtentorial approach was indicated for most pineal region tumors, but surgeon's preference and experience should also be considered. New understanding of the arachnoid membranes of this region may be helpful for tumor resection.

Understanding the mechanisms of glioblastoma at the molecular and structural level is not only interesting for basic science but also valuable for biotechnological application, such as the clinical treatment. In the present study, bioinformatics analysis was performed to reveal and identify the key genes of glioblastoma multiforme (GBM). The results obtained in the present study signified the importance of some genes, such as COL3A1, FN1, and MMP9, for glioblastoma. Based on the selected genes, a prediction model was built, which achieved 94.4% prediction accuracy. These findings might provide more insights into the genetic basis of glioblastoma.

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Matrix proteins are considered to be essential for biomineralization and to be important factors in cranioharyngioma calcification. Osteopontin (OPN) is a noncollagenous, acidic bone-matrix glycoprotein, which binds tightly to hydroxyapatite and appears to form an integral part of the mineralized matrix, probably important to the integrity of cell-matrix interactions. OPN is also a ligand for a cell membrane receptor, CD44v6, which is required for efficient OPN binding. To investigate the role of OPN in craniopharyngioma calcification formation, we studied the involvement of OPN and CD44v6 in craniopharyngiomas. Immunohistochemical staining was used in human craniopharyngiomas to detect the relationship of OPN and degree of calcification, and immunogold localization of OPN was done to identify cell secretory granules. OPN expression was elevated in calcification craniopharyngioma samples. Immunohistochemical staining demonstrated that the OPN expression level was significantly correlated with the degree of calcification (chi(2) = 29.987, P < 0.001); meanwhile, immunoelectron microscopy revealed subcellular sites of OPN presenting in epithelial cells, suggesting that the OPN protein is probably synthesized and secreted by stellate reticulum-like cells and ameloblast-like cells. At the same time, OPN expression was paralleled by cell surface reactivity for CD44v6, an OPN functional receptor. These results suggest that OPN is possibly involved as a core protein in the formation of craniopharyngioma calcification.

BackgroundBeta (β)-human chorionic gonadotropin (β-HCG) is used to confirm the diagnosis and plan treatment of intracranial germinomas. However, the cutoff values of serum β-HCG in diagnosis of intracranial germinomas reported in the literature are inconsistent. To establish an appropriate cutoff value of serum β-HCG for diagnosis of intracranial germinomas, we retrospectively reviewed the records of intracranial tumor patients who received serum β-HCG and α-fetoprotein (AFP) tests for diagnostic purposes at our hospital from 2005 to 2014.MethodsA total of 93 intracranial germinomas and 289 intracranial non-germ cell tumors were included in this study. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of 3 cutoffs (0.1, 0.4, and 0.5 mIU/mL) for diagnosing intracranial germinomas. The serum β-HCG level of intracranial germinoma patients was further analyzed to investigate the effect of metastasis status and tumor location on serum β-HCG level.ResultsThe area under the ROC curve was 0.81 (P < .001), suggesting β-HCG is an effective marker. Of the 3 cutoff values, 0.1 mIU/mL possessed a highest sensitivity (66.67%) and good specificity (91%). Although there was no β-HCG level difference between metastatic and non-metastatic intracranial germinoma patients, the diagnostic rate of metastatic neurohypophyseal germinomas was significantly higher than that of its non-metastatic counterpart (P < .05), implying that the location of the germinoma might need to be considered when β-HCG is used as a marker to predict metastasis.ConclusionsDetermining an optimal cutoff of serum β-HCG is helpful for assisting the diagnosis of intracranial germinoma.

Background: A series of patients harboring pineal region meningiomas were respectively analyzed to explore the origin of these tumors and the true meaning of the term "velum interpositum (VI) meningiomas". Methods: 21 patients with pineal meningiomas underwent operation in Nanfang Hospital of Southern Medical University from January 2005 to December 2016 were retrospectively included to analyze the clinical features, imaging findings and surgical video data of these patients. According to the method of literature, the data of this group were also divided into falcotentorial (FT) meningiomas and VI meningiomas, and the differences between the two types of tumors were compared. Results: Among the 21 cases of tumor, there were 12 cases of FT meningiomas, including 4 cases originating from cerebral falx, 4 cases from tentorium of cerebellum and 4 cases from straight sinus; there were 9 cases of VI meningiomas, 7 of which originated from the arachnoid sleeve of the Galen vein, 1 from the posterior part of the internal cerebral vein and 1 from the posterior surface of the pineal gland. Postoperative pathological examination showed meningiomas in all the 21 patients, including 16 cases of total resection and 5 cases of subtotal resection. Postoperatively limitation of binocular vertical motion was found in 3 cases, homotropic hemianopia in 7 cases, hemiplegia in 1 case and death in 1 case. Conclusions: This study suggests that pineal meningiomas are more suitable to be described by FT meningioma and meningiomas of the arachnoid of the pineal region by analyzing the origin of tumors. The term "VI meningiomas" can only reflect a part of meningiomas of the arachnoid of the pineal region. Before the removal of pineal meningiomas, more attention should be paid to the effects of the two types of tumors on the Galen vein and the straight sinus, and the establishment of venous collateral circulation.